Antimitotic compounds interfere with the dynamic assembly and disassembly of α- and β-tubulin into microtubules causing cells to arrest in mitosis. Prolonged arrest in mitosis eventually leads to cell death, often by apoptosis. Two chemical classes of antimitotic agents, the vinca alkaloids (vinblastine, vincristine, and vinorelbine) and the taxanes (paclitaxel and docetaxel), are clinically useful anticancer drugs. Most known antimitotic agents induce mitotic arrest by inhibiting the polymerization of tubulin into microtubules. This is the mechanism of the vinca alkaloids and rhizoxin.
Paclitaxel was the first chemical entity shown to cause mitotic arrest by stabilizing microtubules against depolymerization. Four additional chemotypes that have paclitaxel-like effects were later identified. These include the myxobacterium metabolites epothilones A and B, the marine sponge metabolites discodermolide, laulimalide, and isolaulimalide, and the soft coral terpenoid, eleutherobin (shown below). Ojima et al. (1999) Proc. Natl. Acad. Sci. USA 96:4256–4261, proposed a common pharmacophore for the microtubule stabilizing compounds that effectively accommodates nonataxel, paclitaxel, discodermolide, eleutherobin, and the epothilones. This model predicts that three regions of eleutherobin (boxes A, B, and C below) are important for binding to tubulin (Me=methyl; Ac=acetyl).